Genetic interaction is associated with lower metabolic connectivity and memory impairment in clinically mild Alzheimer's disease.
Genes Brain Behav
; 18(5): e12490, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-29883038
ABSTRACT
Metabolic connectivity as showed by [18F] fluorodeoxyglucose (FDG) positron emission tomography (FDG-PET) reflects neuronal connectivity. The aim of this study was to investigate the genetic impact on metabolic connectivity in default mode subnetworks and its clinical-pathological relationships in patients with Alzheimer's disease (AD). We separately investigated the modulation of 2 default mode subnetworks, as identified with independent component analysis, by comparing APOE-ε4 carriers to noncarriers with AD. We further analyzed the interaction effects of APOE (APOE-ε4 carriers vs noncarriers) with PICALM (rs3851179-GG vs rs3851179-A-allele carriers) on episodic memory (EM) deficits, reduction in cerebral metabolic rate for glucose (CMRgl) and decreased metabolic connectivity in default mode subnetworks. The metabolic connectivity in the ventral default mode network (vDMN) was positively correlated with EM scores (ß =0.441, P < .001). The APOE-ε4 carriers had significantly lower metabolic connectivity in the vDMN than the APOE-ε4 carriers (t(96) = -2.233, P = .028). There was an effect of the APOE-PICALM (rs3851179) interactions on reduced CMRgl in regions of vDMN (P < .001), and on memory deficits (F3,93 =5.568, P = .020). This study identified that PICALM may modulates memory deficits, reduced CMRgl and decreased metabolic connectivity in the vDMN in APOE-ε4 carriers. [18F] FDG-PET-based metabolic connectivity may serve a useful tool to elucidate the neural networks underlying clinical-pathological relationships in AD.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
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Proteínas Monoméricas de Montagem de Clatrina
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Doença de Alzheimer
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Conectoma
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Memória
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
Genes Brain Behav
Ano de publicação:
2019
Tipo de documento:
Article